Aromatase Inhibitors (AI) vs. SERMs - Differences. Which one to choose?

Aromatase is an enzyme that is essential to complete estrogen biosynthesis. It is responsible for the aromatization of androgens (e.g., testosterone or androstenedione) into estrogens.


Selective estrogen receptor modulators (SERMs) are medications that alter the activity of estrogen receptors by preventing estrogen from binding to them. Unlike aromatase inhibitors, they do not directly decrease estrogen levels and prevent testosterone to estrogen conversion. Instead, SERMs selectively block estrogen activity in the body, which stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the hypothalamus-pituitary. Athletes commonly use SERMs to prevent side effects caused by high estrogen levels and to restore the full functioning of the HPT axis during post-cycle therapy. In medicine, they are used to treat tumors and hypogonadism.

The most common SERMs are:

- Clomiphene Citrate (clomid)

- Tamoxifen (nolvadex)

Aromatase Inhibitors (AIs) are a class of drugs used to inhibit the conversion of androgens, mainly testosterone, to estrogens, by deactivating the aromatase enzyme, which catalysis the process. Athletes use them throughout AAS cycle to control estrogen levels. Although through a different mechanism, AIs also promote testosterone secretion and during PCT restoration of the activity of HPT axis.

The most common AIs are:

- Exemestane (Aromasin)

- Anastrozole

- Letrozole

Differences 

Aromatase inhibitors and SERMs plays a completely different role during an AAS cycle or PCT. AIs are used throughout the cycle to reduce estrogen levels resulting from testosterone to estrogen conversion. In PCT, they help to restore the proper functioning of HPT axis; however, requires stacking with SERMs. On the other hand, SERMs are mainly used during PCT to efficiently restore HPT axis functioning. During an AAS cycle, they're rarely used to control increased estrogen activity resulting from the intake of highly aromatising compounds like metanabol, especially in men prone to estrogenic side effects like gynecomastia.

Which SERM to choose?

CLOMIPHENE CITRATE
Common choice among endocrinologists to treat hypogonadism and the most popular SERM among athletes during PCT. It effectively restores the functions of HPT axis. Nevertheless, many men experience adverse effects like headaches, upset stomach or mental depression. 

TAMOXIFEN
While not as popular as Clomid, this medication has a similar potency and is often used in PCT protocols, including in Dr. Michael Scally's updated Power PCT protocol. It can be taken alongside Clomiphene or on its own to restore HPTA functions during PCT and treat hypogonadism. Compared to Clomiphene, it is typically associated with fewer side effects. In my opinion, it's a much better choice due to more user-friendly activity in the body, although it still depends on individual predispositions.

Which AI to choose?

EXEMESTANE
Exemestane is a great option as it doesn't cause estrogen rebound after its half-life, helps improve the LDL-HDL ratio, and significantly reduces SHBG. Taking a single 25mg dose can reduce estrogen levels by around 60%. Many people opt to take a 12.5mg dosage every four days for the entire duration of a 500mg testosterone per week cycle. However, the dosage should be determined individually as the rate of aromatization depends on various factors such as body fat, diet, genetic predispositions, current total testosterone level, free testosterone, and SHBG levels.

ANASTROZOLE
If exemestane is unavailable, anastrozole can serve as a viable option. Taking 1mg of anastrozole can decrease estrogen levels by roughly 50%. However, it must be taken more frequently than exemestane since estrogen levels can increase after two days. The recommended dosage is typically 0.5mg every three days. It's important to note that anastrozole provides no additional benefits compared to exemestane.

.
LETROZOLE
The most potent aromatase inhibitor, capable of reducing estrogen levels to zero with a 2.5mg dosage (1 tablet). While it can be effective in reversing early stages of gynecomastia and lowering SHBG, it may worsen the LDL - HDL ratio and cause numerous side effects like tiredness or worsened mood. Using letrozole requires responsible and cautious use. Its potential to significantly reduce estrogen levels is so high that during a regular AAS cycle, best to avoid using it altogether.